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Streptococcus pyogenes (Group A Strep)

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Streptococcus pyogenes (Group A Strep)

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Streptococcus pyogenes (Group A Strep)

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A regimen of (antibiotic) for 10 days is the treatment of choice for Streptococcus pyogenes (group A streptococcal) infections.

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USMLE® Step 1 style questions USMLE

16 questions

USMLE® Step 2 style questions USMLE

11 questions
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 A 34-year-old man presents to the emergency department for evaluation of pain in the right lower extremity. The patient was running on the beach without shoes over the past weekend and sustained a small laceration to the bottom of the foot. Over the past 24 hours, he has been experiencing severe pain and swelling of the foot to the point that he is unable to bear weight. He is otherwise healthy and does not smoke, consume alcohol, or use illicit substances. Temperature is 38.6°C (101.5°F), pulse is 109/min, respirations are 22/min, and blood pressure is 131/72 mmHg. On physical examination, a 3 cm x 3 cm area of erythema is noted on the underside of the right foot. The patient is exquisitely tender to palpation over the entire aspect of the right foot extending to the mid tibia. A radiograph of the right foot is obtained and demonstrates the following finding:



Reproduced from: Radiopaedia

Which of the following is the most appropriate treatment for this patient’s clinical condition?  

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Transcript

Content Reviewers:

Viviana Popa, MD

Streptococcus pyogenes, sometimes called Strep pyogenes, can be broken down into “strepto” which means chain, “coccus”, which refers to round shape, “pyo” which means pus, and “genes” which refers to forming.

So, Strep pyogenes are round bacteria that grow in chains, responsible for a number of infections that often present with pus. Strep pyogenes are also called Group A Strep – GAS - in Lancefield classification developed by American microbiologist Rebecca Lancefield. 

Ok now, Strep pyogenes has a thick peptidoglycan cell wall, which takes in purple dye when Gram-stained - so this is a gram-positive bacteria.

It’s non-motile and doesn’t form spores, and it’s also a facultative anaerobe, meaning it can survive in both aerobic and anaerobic environments.

Finally, Strep pyogenes is catalase negative, meaning it doesn’t make an enzyme called catalase. 

However, unlike other common cocci like Enterococci, Strep pyogenes is pyrrolidonyl arylamidase positive, because it makes an enzyme called L-pyrrolidonyl arylamidase.

To test for this, a small sample is taken from a suspected bacterial colony, and then inoculated to a disk pad that’s embedded with pyrrolidonyl beta naphthylamide - another joy of a word.

With Strep pyogenes, pyrrolidonyl arylamidase hydrolyzes pyrrolidonyl beta—naphthylamide to produce beta-naphthylamide.

Try saying that 3 times fast! Finally, another reagent called N-methylamino-cinnamaldehyde is added to the disk, and it reacts with beta—naphthylamide, resulting in a bright red color that confirms Strep pyogenes is pyrrolidonyl arylamidase positive.

When cultivated on a medium called blood agar, Strep pyogenes colonies cause  beta-hemolysis, also called complete hemolysis. That’s because Strep pyogenes makes toxins known as streptolysins, which hydrolyze the hemoglobin in red blood cells to transparent yellow color byproducts. 

But some other Streptococcus species, like Strep agalactiae, are also beta-hemolytic. So a bacitracin test is done to distinguish Strep pyogenes.

That’s when a disk of bacitracin is added to the blood agar. Strep pyogenes is bacitracin sensitive, so the colonies die off, whereas with Strep agalactiae, the colonies remain intact.  

Now, Strep pyogenes has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.

So first, Strep pyogenes is encapsulated, meaning it’s covered by a polysaccharide layer called a capsule.

And on the capsule, there are adherence proteins such as lipoteichoic acid, Streptococcus fibronectin binding protein - or Sfbl for short, and M protein, which help Strep pyogenes attach to the host cells, like those in the skin or the pharyngeal mucosa. 

Then, Strep pyogenes uses toxins like hyaluronidase, which destroys hyaluronic acid, a cement substance that keeps cells of the connective tissues and blood vessels tightly linked.

Destruction of hyaluronic acid results in local inflammation, and enables the bacteria to spread to the bloodstream.

In the bloodstream, Strep pyogenes uses streptolysin O and S, which are toxins that cause hemolysis, or red blood cell destruction.

It also uses erythrogenic toxins, that are also called Streptococcal Pyrogenic Exotoxins, or Spe for short, which come in 3 flavors: SpeA, SpeB, and SpeC.

This leads to increased hemolysis in the dermal and submucosal blood capillaries. What is more, SpeA and SpeC are superantigens, meaning they don’t need to be eaten up and processed by an antigen-presenting cell such as a macrophage to generate an immune response from T-cells.

Instead, they interact immediately with the class II MHC molecule on the surface of the macrophage, forming a superantigen-MHC complex, which then interacts with the T-cell receptor and stimulates up to 30% of the entire T- cell population.

This is 300 times powerful the conventional antigens, and it stimulates the release of a whole bunch of inflammatory cytokines.

Specifically, this is called a cytokine storm, and it can result in toxic shock syndrome or TSS, which happens when a such  cytokine storm triggers widespread systemic vasodilation, making blood pressure drop, which leads to poor perfusion of vital organs.

From the bloodstream, strep pyogenes bacteria can spread to other organs, like the lungs, causing pneumonia or lung abscesses, or the heart, where they form clumps called vegetations on the heart valves, causing infective endocarditis.

Alternatively, if they spread to central nervous system, they can cause brain abscesses, or meningitis.

Surprisingly, despite all that powerful arsenal, Strep pyogenes can actually peacefully colonize the skin, the mucosa of the pharynx or throat, the vagina, and the rectum.

It doesn’t do any harm so long as the immune system keeps them in check, restricting their growth and preventing them from spreading somewhere else in the body.

Problems arise in individuals with weaker immune systems, like infants and the elderly. Other immune-weakening conditions include HIV infection, diabetes, or a malignancy.

In these cases, Strep pyogenes usually gets in the bloodstream through a breach on the skin, a mucosal laceration, or following surgery. 

Most often, Strep pyogenes causes strep pharyngitis also called strep throat, which is the inflammation of the pharyngeal mucosa and tonsils.

Strep pharyngitis may also be associated with scarlet fever, which is when intracapillary hemolysis results in a bright-red skin rash.

When Strep pyogenes infects the epidermis, it causes impetigo, which are superficial skin lesions that look like honey clusters.